SBP Level May Be Key to Setting Blood Pressure Treatment Goals for Diabetes

The review of 49 trials enrolling 73,738 participants, published online February 25 in the BMJ, “strongly supports blood-pressure treatment in people with diabetes mellitus if SBP is more than 140 mm Hg.”

Mattias Brunström and Bo Carlberg, MD, of the department of public health and clinical medicine, Umeå University, Sweden, noted that “intensive blood pressure lowering treatment using antihypertensive drugs may be harmful for people with diabetes and a systolic blood pressure less than 140 mm Hg.”

The systematic review and meta-analyses of the randomized controlled trials was done to assess the effect of antihypertensive treatment on mortality and cardiovascular morbidity in people with diabetes mellitus, at different blood pressure levels.

The data sources consisted of CENTRAL, Medline, Embase, and BIOSIS were searched using highly sensitive search strategies. When data required according to the protocol were missing but trials were potentially eligible, the researchers, pharmaceutical companies, and authorities were contacted.

Since the publication of SPRINT, there have been discussions regarding whether to lower blood-pressure targets in general and whether the results from SPRINT should be extrapolated to people with diabetes. The results suggest that the current recommendation to treat people with diabetes to less than 140 mm Hg is appropriate and should not be changed because of SPRINT.

The eligibility criteria were randomized controlled trials, including 100 or more people with diabetes mellitus, treated for 12 months or more, comparing any antihypertensive agent against placebo, two agents against one, or different blood pressure targets.

The results of 49 trials, including 73,738 participants, were included in the meta-analyses. Most of the participants had type 2 diabetes. If baseline systolic blood pressure was greater than 150 mm Hg, antihypertensive treatment reduced the risk of all cause mortality (relative risk 0.89, 95% confidence interval 0.80 to 0.99), cardiovascular mortality (0.75, 0.57 to 0.99), myocardial infarction (0.74, 0.63 to 0.87), stroke (0.77, 0.65 to 0.91), and end stage renal disease (0.82, 0.71 to 0.94). If baseline systolic blood pressure was 140-150 mm Hg, additional treatment reduced the risk of all cause mortality (0.87, 0.78 to 0.98), myocardial infarction (0.84, 0.76 to 0.93), and heart failure (0.80, 0.66 to 0.97). If baseline systolic blood pressure was less than 140 mm Hg, however, further treatment increased the risk of cardiovascular mortality (1.15, 1.00 to 1.32), with a tendency towards an increased risk of all cause mortality (1.05, 0.95 to 1.16). Meta-regression analyses showed a worse treatment effect with lower baseline systolic blood pressures for cardiovascular mortality (1.15, 1.03 to 1.29 for each 10 mm Hg lower systolic blood pressure) and myocardial infarction (1.12, 1.03 to 1.22 for each 10 mm Hg lower systolic blood pressure). Patterns were similar for attained systolic blood pressure.

This systematic review and meta-analyses confirms that blood pressure lowering treatment is associated with reduced mortality and cardiovascular morbidity in people with diabetes, if systolic blood pressure (SBP) before treatment was more than 140 mm Hg. If SBP is less than 140 mm Hg, however, it was found that there was no benefit, but potential harm, with an increased risk of cardiovascular death. This fits well with the analyses stratified by attained SBP. Treatment reduced the risk of all cause mortality, myocardial infarction, stroke, and heart failure, if SBP was treated to 130-140 mm Hg, but was associated with a non-significant increase in all cause and cardiovascular mortality if SBP was lowered to less than 130 mm Hg. The results are further supported by meta regression analyses showing that treatment effect on cardiovascular mortality and myocardial infarction is worse for each unit decrease in baseline SBP, and harmful below certain levels.

This systematic review and meta-analyses included a large amount of previously unpublished data, thereby increasing precision compared with previous research. Results from the analyses stratified by baseline SBP are largely consistent with those stratified by attained SBP. The interaction between blood pressure and treatment effect is reproducible across exposure variables and outcomes, indicating a robust dose-response relation. Together with a possible biological mechanism, the results suggest that SBP before treatment modifies the effect of treatment in a causal way.

The results are important both conceptually for research on hypertension and for clinicians. Firstly, it was shown that not only the absolute, but also the relative benefit of blood pressure lowering is attenuated at lower blood pressures. This suggests that the linear relation between blood pressure and cardiovascular disease seen in some observational studies cannot be extrapolated to assumed benefit of treatment. Stretching this further, it was shown that based on randomized comparisons, that treatment below a certain blood pressure level might be harmful. Secondly, and contrary to what has previously been recommended, these results, combined with those from the SPRINT trial, suggest that blood pressure treatment goals should be less aggressive in people with diabetes than without diabetes. This review strongly supports blood pressure treatment in people with diabetes if SBP is more than 140 mm Hg. If SBP is already less than 140 mm Hg, however, adding additional agents might be harmful.

From all the results it was concluded that, antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic blood pressure more than 140 mm Hg. If systolic blood pressure is less than 140 mm Hg, however, further treatment is associated with an increased risk of cardiovascular death, with no observed benefit.

Practice Pearls:

People with diabetes are at increased risk of cardiovascular disease and often have concomitant hypertension.

Antihypertensive treatment reduces the risk of cardiovascular disease in people with diabetes, but the optimal blood pressure level has been debated.

In people with diabetes and a systolic blood pressure of more than 140 mm Hg, antihypertensive treatment is associated with a reduced risk of mortality and cardiovascular disease.

In people with diabetes and a systolic blood pressure of less than 140 mm Hg, however, antihypertensive treatment is associated with an increased risk of cardiovascular death.

The interaction between systolic blood pressure before treatment and the treatment effect is significant.

Zanchetti A, Grassi G, Mancia G. When should antihypertensive drug treatment be initiated and to what levels should systolic blood pressure be lowered? A critical reappraisal. J Hypertens 2009;27:923-34.doi:10.1097/HJH.0b013e32832aa6b5.19381107.

Mancia G. Effects of intensive blood pressure control in the management of patients with type 2 diabetes mellitus in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Circulation 2010;122:847-9.doi:10.1161/CIRCULATIONAHA.110.960120.20733113.